Abstract

Human gut harbors 100 trillion microbes that is intrinsically linked to individual's health and diseases, including cancer. Triterpenoid saponins are present in many plants and are major active components in medicinal plants. Gynostemma pentaphyllum (Gp) is consumed as herbal tea as well as herbal medicine and found to possess anti-cancer effects in ApcMin/+ mice in our study. Here, we would like to address whether Gp saponins (GpS) can affect the gut microbiota in the ApcMin/+ colorectal cancer mouse model, and whether the alteration would have cancer preventive implication.

Using ERIC-PCR and 16S pyrosequencing analysis, we revealed that GpS treatment altered the overall fecal microbiome. Interestingly, it appeared that GpS treatment enhanced the relatively abundance of the beneficial microbes while reduced the potential harmful sulfate- and sulfur-reducing bacteria lineage. The impact of GpS on the gut mucosal environment was also examined. We found GpS improved the gut barrier function by increasing the numbers of Paneth cells, goblet cells, up-regulating the expression of E-cadherin and down-regulating the expression of N-cadherin in the intestine. In addition, GpS down-regulated the protein expression of beta-catenin and the p-STAT3. Furthermore, higher levels of anti-inflammatory and tissue repair-related cytokines as well as arginase I, but lower level of iNOS expression were found in GpS-treated ApcMin/+ mice. Altogether, GpS might affect the host-microbe interactions by regulating the gut microbial ecosystem and modulating the intestinal mucosal environment, which might contribute to its cancer preventive effect observed in the ApcMin/+ mice.

This study was supported by Macau Science and Technology Development Fund 015/2014/A1 and Research Grants Council of Hong Kong under GRF260413 to WL Wendy Hsiao.